Impact of Precision Dosing on Patient Care
In the realm of modern medicine, precision dosing stands as a transformative approach.
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Precision medicine promotes patient care by connecting physicians and patients and improves the dynamics between all teams involved from nurses, pharmacists, infectious disease specialists and more.
Drilling down on all components, it is important to look closer at precision dosing, which includes therapeutic drug monitoring (TDM). TDM utilizes patient data and laboratory results to estimate a patient's ability to absorb, distribute, metabolize and excrete a drug from their system. Using a clinically validated population model, algorithms can adjust the pharmacokinetic and/or pharmacodynamic parameters so that a patient-specific, individualized drug model is built. This individual model is then used to provide a patient-specific dosing recommendation to reach a therapeutic target. Clinical pharmacists have taken on a new role as the adoption of precision medicine increases. They are now a key point of care in the patient journey.
Expanding into a strategic role in infectious disease, transplant medicine, cardiovascular and coagulation management, oncology, pediatrics and more, utilizing precision dosing has become a crucial element of every healthcare team.
Collaboration between clinical pharmacists and healthcare providers establishes a robust framework to improve patient care. With the advent of clinical pharmacists on the ward, the landscape of pharmacy has witnessed a transformation. Clinical pharmacists actively engage in clinical rounds alongside physicians, proffering valuable insights and recommendations for the best possible patient outcomes.
Physicians, responsible for prescribing medicines, rely on the expertise of pharmacists to ensure the optimal and rational use of drugs. Clinical pharmacists meticulously review prescriptions to verify their appropriateness, encompassing critical factors such as indications, drug selection, dosage, duration and timing. Should any deviations arise, pharmacists promptly intervene, informing the prescriber and diligently documenting these interventions. The successful alignment between physicians and pharmacists, acknowledging the impact of these interventions, solidifies the undeniable outcome of enhanced therapy. This harmonious synergy underscores the pivotal role pharmacists play in precision dosing, reinforcing the pursuit of optimal patient care.
From drug development to clinical trials
The impact of real-world patient data is now being realized in the realm of clinical trials. With the advancements in technology and data science, we are witnessing a paradigm shift toward the customization of starting and on-treatment doses, maximizing the potential for individual benefit. As this approach continues to gain momentum, the clinical utility of a vast array of drugs will be substantially enhanced. Though the pursuit of precision dosing may introduce incremental complexity, the amplified therapeutic advantages will overshadow any associated intricacies. Consequently, it should be the new standard for drug development, rendering the antiquated one-dose-for-all approach unacceptable.
Traditionally, drug development has relied on identifying a single recommended dose level that provides satisfactory efficacy with relative safety for the patient population. This approach satisfies the regulatory requirements and affords simplicity in clinical practice.1,2 However, the evolution of technology empowers us to tailor doses to the unique characteristics of each patient, addressing the inherent variability in drug response associated with fixed doses. The shifting expectations of the FDA, patients, prescribers and payers demand this evolution. Therefore, drug developers must undergo a transformative process to embrace precision dosing as the cornerstone of new therapeutic interventions.
Integrating dose comparison studies within phase 2 trials holds immense potential for refining the design of subsequent phase 3 trials.3 By informing the selection doses to be studied this could pave the way for prospectively defining dose escalation or reduction strategies during phase 3 trials.3 For example, dose comparison studies may reveal that while multiple doses achieve anti-tumor responses, a significant portion of patients either show no response to lower doses or struggle with tolerating the higher dose. Adaptive clinical trial protocols, accommodating dose adjustments under specific conditions (e.g., lack of response to initial dose coupled with tolerance for higher doses; positive response with severe side effects) could facilitate the inclusion of appropriate dose modification strategies in labeling claims. Indeed, this approach has been successfully implemented for several oncology drugs.
Therapeutic window driving the need for precision medicine
In the realm of modern medicine, precision dosing stands as a transformative approach, tailoring drug doses to optimize the benefit-to-risk ratio for each patient. While acknowledging the importance of adjusting doses for well-established factors like age, ethnicity, organ failure or drug interactions, it is imperative to recognize that the majority of drugs today are not developed with precision dosing in mind. Instead, the traditional focus lies in identifying a single dose level that can be universally applied to all patients – a "one dose fits all" paradigm. This approach, commendable for its simplicity in drug development, manufacturing and clinical use, has proven its efficacy over the decades, particularly for drugs with wide therapeutic windows.4 By administering doses higher than what some patients might actually need, yet still well tolerated, the inherent variability in patient responses is effectively mitigated. The “one dose fits all” approach has undoubtedly served its purpose, allowing for widespread access to medications that deliver substantial therapeutic benefits.4
On the other end of the spectrum, certain drugs like warfarin, insulin and anesthesia pose a distinct challenge. These drugs inhabit a therapeutic window unique for each patient, but significantly narrower when compared to the substantial variability across the entire population. In this scenario, the conventional approach fails to provide an acceptable balance of efficacy and safety for all individuals.4
In March 2020, the 2020 vancomycin dosing guidelines from four leading pharmacy and infectious diseases professional societies – ASHP, IDSA, PIDS and SIDP – were published in advance online in the American Journal of Health-System Pharmacy.
One of the biggest changes from the last vancomycin dosing guideline published in 2009 is that experts recommend moving from the traditional trough-based dosing approach and transitioning to area under the curve (AUC)-guided dosing for both adults and pediatrics who have suspected or definitive serious MRSA infections. By moving beyond trough measurements and embracing AUC-guided dosing, healthcare professionals can optimize therapeutic efficacy while minimizing the potential for adverse outcomes. Such a paradigm shift in dosing strategies reflects our pursuit of precision medicine and propels us into a new era of patient-centered care.
What to expect moving forward?
TDM is a critical component that serves as the foundation of personalized treatment. However, the current state of drug monitoring poses significant challenges, often burdened by laborious processes, time constraints and the complexities of working within a limited resource and budget framework in a highly regulated environment. The traditional landscape of therapeutic drug monitoring is riddled with inefficiencies. Oftentimes, healthcare professionals find themselves juggling multiple moving parts to maintain accuracy in their dose adjustments. These tasks demand considerable time and attention, diverting healthcare providers from focusing on what truly matters – providing optimal care to their patients.
As we navigate the realms of technology and innovation, precision dosing platforms emerge as the catalysts for change in the landscape of TDM. They offer a lifeline to healthcare professionals burdened by the complexities of the existing system, empowering them to deliver superior patient care with enhanced efficiency and accuracy. The time for a paradigm shift in TDM is now, and it starts with embracing precision dosing platforms as the vehicles that will drive us toward a future of personalized, patient-centric healthcare.
About the author:
Sharmeen Roy, PharmD, BCPS, is chief strategy and science officer at DoseMe.
1. Pharmacokinetics in patients with impaired hepatic function—study design, data analysis, and impact on dosing and labeling. U.S. Food and Drug Administration. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pharmacokinetics-patients-impaired-hepatic-function-study-design-data-analysis-and-impact-dosing-and Accessed August 16, 2023.
2. Pharmacokinetics in patients with impaired renal function — study design, data analysis, and impact on dosing. U.S. Food and Drug Administration. . https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pharmacokinetics-patients-impaired-renal-function-study-design-data-analysis-and-impact-dosingPublished September 2020. Accessed August 16, 2023.
3. Wang L, Maxfield K, Guinn D, Madabushi R, Zineh I, Schuck RN. A systematic assessment of US Food and Drug Administration dosing recommendations for drug development programs amenable to response‐guided titration. Clin Pharmacol Ther. 2021;109(1):123-130. doi: 10.1002/cpt.2068
4. Peck RW. Precision dosing: an industry perspective. Clin Pharmacol Ther. 2021;109(1):47-50. doi: 10.1002/cpt.2064